Saturated Fatty Acid-Induced Insulin Resistance Is Associated With Mitochondrial Dysfunction in Skeletal Muscle Cells

Autor(es)

Hirabara, Sandro M. ^{[1, 2, 3]} ; Curi, Rui ^[1] ; Maechler, Pierre ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil

^[2] Cruzeiro Univ, Inst Phys Act Sci & Sportes, Postgrad Program Human Movement Sci, Sao Paulo - Brazil

^[3] Univ Geneva, Univ Med Ctr, Dept Cell Physiol & Metab, Geneva 4 - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 222, n. 1, p. 187-194, JAN 2010.
• Citações Web of Science: 96

Resumo

Increased plasma levels of free fatty acids (FFA) occur in states of insulin resistance such as obesity and type 2 diabetes mellitus. These high levels of plasma FFA are proposed to play an important role for the development of insulin resistance but the mechanisms involved are still unclear. This study investigated the effects of saturated and unsaturated FFA on insulin sensitivity in parallel with mitochondrial function. C2C12 myotubes were treated for 24 h with 0.1 mM of saturated (palmitic and stearic) and unsaturated (oleic, linoleic, eicosapentaenoic, and docosahexaenoic) FFA. After this period, basal and insulin-stimulated glucose metabolism and mitochondrial function were evaluated. Saturated palmitic and stearic acids decreased insulin-induced glycogen synthesis, glucose oxidation, and lactate production. Basal glucose oxidation was also reduced. Palmitic and stearic acids impaired mitochondrial function as demonstrated by decrease of both mitochondrial hyperpolarization and ATP generation. These FFA also decreased Akt activation by insulin. As opposed to saturated FFA, unsaturated FFA did not impair glucose metabolism and mitochondrial function. Primary cultures of rat skeletal muscle cells exhibited similar responses to saturated FFA as compared to C2C12 cells. These results show that in muscle cells saturated FFA-induced mitochondrial dysfunction associated with impaired insulin-induced glucose metabolism. J. Cell. Physiol. 222: 187-194, 2010. (C) 2009 Wiley-Liss, Inc. (AU)

• Processo FAPESP: 08/01177-3 - Função mitocondrial e resistência à insulina muscular: papel dos ácidos graxos e da atividade física
• Beneficiário: Sandro Massao Hirabara
• Modalidade de apoio: Auxílio à Pesquisa - Regular